It is well known to employ medicinal agents in the treatment of persons suffering from diabetes, hyperglycemia and obesity
Ainsworth et al, U.S. Pat. No. 4,478,849, disclose secondary amine compounds having the general formula (I): ##STR4## wherein R.sub.1 is a hydrogen, fluorine or chlorine atom or a hydroxyl, hydroxymethyl, methyl, methoxyl, amido, formamido, acetamido, methylsulfonylamido, nitro, benzyloxy, methylsulfonylmethyl, ureido, trifluoromethyl, or methoxybenzylamino group; R.sub.2 is a hydrogen, fluorine or chlorine atom or a hydroxyl group; R.sub.3 is a hydrogen or chlorine atom or a hydroxyl group; R.sub.4 is a carboxylic acid group or a salt, ester or amide thereof; R.sub.5 is a hydrogen, chlorine or fluorine atom or a methyl, methoxyl, or hydroxyl group or a carboxylic acid group or a salt, ester or amide thereof; R.sub.6 is a hydrogen atom or a methyl or propyl group; X is an oxygen atom or a bond; and Y is an alkylene group of up to 6 carbon atoms or a bond, which have anti-obesity and/or anti-hyperglycemic activity
Ainsworth et al, U.S. Pat. No. 4,396,627, disclose secondary amine compounds of the formula (II): ##STR5## wherein R.sub.1, R.sub.2 and R.sub.3 are as defined in relation to formula (I) or each independently represents a bromine atom; R.sub.4 is an alkyl group of 1 to 10 carbon atoms substituted by a hydroxyl, lower alkoxyl, oxo, lower acyloxy or OCH.sub.2 CO.sub.2 H group or lower alkyl ester thereof; R.sub.5 is a hydrogen, chlorine or fluorine atom or a methyl, methoxyl or hydroxyl group or a carboxylic acid group or a salt, ester or amide thereof; R.sub.6 is a hydrogen atom or a methyl, ethyl or propyl group; R.sub.7 is a hydrogen atom or a methyl, ethyl, or propyl group; X is an oxygen atom or a bond; and Y is an alkylene group of up to six carbon atoms or a bond; which are useful in reducing high blood glucose and lipid levels in humans and animals.
Ainsworth et al, U.S. Pat. No. 4,385,066 disclose arylethanol amine derivatives of the formula (III): ##STR6## wherein R.sub.1 and R.sub.2 are hydrogen or methyl; n is 1, 2 or 3; and Z is alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, halogen or hydrogen; useful in treating obesity and/or hyperglycemia and/or inflammation in mammals.
Ferris, U.S. Pat. No. 4,341,793 discloses secondary amine compounds of the formula (IV): ##STR7## wherein A.sub.1 and A.sub.2 are hydrogen or methyl; n is 1, 2 or 3; and R is hydrogen, chlorine, bromine, hydroxy, nitro, amino or trifluoromethyl; which are useful as antihyperglycemia agents or anti-obesity agents.
Smith et al., U.S. Pat. No. 4,309,443, disclose cinnamic acid derivatives of the formula (V): ##STR8## wherein R.sub.1 and R.sub.2 and R.sub.3 are as defined in relation to formula (II); R.sub.4 is a hydrogen, chlorine or fluorine atom or a methyl, methoxyl or hydroxyl group or a carboxylic acid group or a salt, ester or amide thereof; R.sub.5 and R.sub.6 are a hydrogen atom or methyl group; R.sub.7 and R.sub.8 are a hydrogen atom or methyl or ethyl group; X is an oxygen atom or a bond; and Y is an alkylene group of up to 5 carbon atoms; which have been found to possess anti-obesity and/or anti-hyperglycemia activity.
Duckworth, U.S. Pat. No. 4,382,958, disclose secondary amine compositions of the formula (VI): ##STR9## wherein each of R.sub.1 and R.sub.2 are hydrogen, methyl or ethyl; R.sub.3 is hydrogen, fluorine, chlorine, bromine or trifluoromethyl; each of R.sub.4 and R.sub.5 is hydrogen, fluorine, chlorine, bromine, alkyl having 1 to 6 carbon atoms, or alkoxy having 1 to 6 carbon atoms; n is 1 or 2; and X is straight or branched alkylene having 1 to 12 carbon atoms; which are anti-obesity, hypoglycemia, anti-inflammatory and platelet aggregation inhibiting agents.
Ainsworth et al., U.S. Pat. No. 4,654,371, disclose secondary amine compounds of the formula (VII): ##STR10## wherein R.sub.15 is a hydrogen atom or a methyl group; R.sub.16 is a hydrogen atom or a methyl group and m is 1; useful in treating obesity and hyperglycemia in humans or animals
Ikezaki et al., U.S. Pat. No. 4,490,392 disclose benzylalcohol derivatives of the formula (VIII): ##STR11## wherein R is hydroxy, benzyloxy, halogen or alkoxy having 1 to 4 carbon atoms and Ring A is monomethoxyphenyl, dimethoxyphenyl, trimethoxyphenyl or 3,4-methylenedioxyphenyl; which are useful as anti-diabetic agents.
Ferris, U.S. Pat. No. 4,432,993 discloses 2-(2-benzofuranyl)ethanolamine derivatives of the formula (IX): ##STR12## wherein R.sub.1 is hydrogen or methyl; R.sub.2 is hydrogen or methyl; R.sub.3 is hydroxy, hydroxy(C.sub.1 -C.sub.6)alkoxy, benzyloxy or a group X-Y-Z wherein (i) X is a bond or oxygen, Y is a C.sub.1 -C.sub.6 straight or branched alkylene, and Z is hydrogen or carboxy; or (ii) X is a bond or --O--CH.sub.2 --, Y is a C.sub.2 -C.sub.6 straight or branched alkenylene and Z is carboxy; R.sub.4 is hydrogen, hydroxy, halogen, C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.6 alkoxy; and n is 1, 2 or 3; which have anti-obesity, hypoglycemia, anti-inflammatory, and platelet-aggregation inhibiting activity.
Ainsworth et al., U.S. Pat. No. 4,338,333 disclose ethanamine derivatives of the formula (X): ##STR13## wherein R.sub.1, R.sub.2 and R.sub.3 are as defined in relation to formula (I) or each independently represent a bromine atom; R.sub.4 is a hydrogen atom or methyl group; R.sub.5 is a hydrogen atom or methyl group; R.sub.6 is a hydrogen, fluorine or chlorine atom or a methyl, methoxyl or hydroxy group; X is an oxygen atom or a bond; Y is an alkylene group of up to 6 carbon atoms or a bond; and Z is an alkylene, alkenylene or an alkynylene group of up to 10 carbon atoms; which possess anti-obesity and anti-hyperglycemia properties.
Ikezaki et al., U.S. Pat. No. 4,032,575 disclose benzylalcohol amine derivatives of the formula (XI): ##STR14## wherein Ring A is monohydroxyphenyl; which induce a decrease in blood sugar levels when Ring A is 2-hydroxyphenyl.
Holloway et al., U.S. Pat. No. 4,772,631, disclose phenoxyacetic acid ethers of the formula (XII): ##STR15## wherein R.sub.1 is hydrogen or fluorine; R.sub.2 and R.sub.3 are hydrogen or alkyl having 1 to 3 carbon atoms; Z is CH.sub.2 OH or a group --COR.sub.4 in which R.sub.4 is OH, NH.sub.2 or alkoxy having 1 to 6 carbon atoms; which are useful in treating obesity and related conditions.
Philion, U.S. Pat. No. 4,751,246 disclose benzenemethanol and ethylamine compounds of the formula (XIII): ##STR16## wherein R.sub.1, R.sub.2 and R.sub.3 are independently hydrogen or lower alkyl; n is an integer from 1 to 3; Ar is phenyl, methylenedioxyphenyl or phenyl having from 1 to 3 substituents selected from the group consisting of halo, lower alkyl, hydroxy and lower alkoxy; R is lower alkyl; and Y is hydrogen, lower alkyl, lower alkoxy, lower alkyl; lower alkanoyl, aroyl, benzenesulfonyl or toluenesulfonyl; which are useful as anti-hypertensive agents.
It has now been discovered that a group of novel substituted 5-(2-((2-aryl-2-hydroxyethyl)amino) propyl)-1,3-benzodioxoles possess vastly increased anti-hyperglycemia and anti-obesity properties with greater .beta..sub.3 selectivity in comparison with the prior art compounds. The compounds are therefore useful in treating diabetes, hyperglycemia and obesity, exhibiting minimal side effects, i.e. heart rate increase and muscle tremor in humans and animals, when formulated into pharmaceutical compositions.